γ-Secretase modulators: current status and future directions.

Prog Med Chem

Department of BioPharmacology, Discovery Research, Neuroscience and General Medicine Product Creation Unit, Eisai Ltd., EMEA Knowledge Centre, Mosquito Way, Hatfield, United Kingdom.

Published: August 2014


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Article Abstract

This chapter reviews the current status of γ-secretase modulators, highlighting key compounds by each company involved in the area. The review focuses on the three main chemotypes: acids, imidazoles and related derivatives and natural products. A section on chemical biology and ligand-binding site elucidation studies is also included. The primary source of information is drawn from peer reviewed literature as this permits analysis of PK-PD relationships and subsequent comment. Discussion of the patent literature is included for completeness. From this analysis, the key issues and challenges in the area are highlighted. The review concludes with a summary of the clinical development status and comment on future prospects of the field.

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